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Meijuan Huang
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P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P84.07 - Distribution and Therapeutic Outcomes of Intergenic Sequence-ALK Fusion and Coexisting ALK Fusions in Lung Adenocarcinoma Patients (ID 1066)
00:00 - 00:00 | Presenting Author(s): Meijuan Huang
- Abstract
Introduction
ALK-rearranged NSCLC patients show survival benefits from ALK inhibitor. Studies about outcome were mostly focused on EML4–ALK fusion. Here, we performed next-generation sequencing (NGS) of baseline specimens from ALK-positive patients to examine the rearrangement distribution and possible correlation to therapeutic benefit.
Methods
ALK-positive NSCLC patient(determined by immunohistochemistry) were screened at the West China Hospital, and NGS was performed on baseline samples. Clinical information and therapeutic outcomes were collected and retrospectively analyzed.
Results
Among the 89 patients with 22 ALK rearrangements partners, fusions of intergenic sequences with ALK were found in 15 (16.85%). Non-EML4–ALK fusions were present in 18 patients (20.22%), while EML4–ALK fusions in 71 (79.76%). Coexisting rearrangements were present in 16 patients (17.98%). Intergenic–ALK and non EML4–ALK fusions occurred at higher rates in patients with coexisting fusions (62.5% versus 6.85%, and 62.5% versus 10.96%). First-line crizotinib was administered in 41 patients, and the median progression-free survival (mPFS) was 9.7 months. No significant difference in mPFS was found between patients with or without intergenic ALK fusion (12 versus 9.6 months, p = 0.989). In the seven patients who had at least two fusions each, the mPFS was 11.9 months, compared with 9 months among the 24 patients with single (p = 0.336). No significant difference in mPFS was observed between patients with and without EML4–ALK fusions (9.6 versus 12 months, p = 0.924). The hazard ratio(HR) of gender, age and three rearrangements (EML4-, non EML4-, intergenic-ALK) were 0.47, 1.18, 1.09, 1.31, 0.96, respectively.
Table 1 Characteristics of enrolled patients.
Characteristic
Total
(n = 90)
Treatment
P value
Surgery
(n = 46)
Systemic therapy
(n = 44)
Age (median [range], years)
51 (29-78)
52.5 (30-78)
49 (29-70)
0.396
Gender (cases, %)
0.404
Male
47 (52.2)
26 (56.5)
21 (47.7)
Female
43 (47.8)
20 (43.5)
23 (52.3)
Smoking status (cases, %)
0.185
Smoker
6 (6.7)
1 (2.2)
5 (11.4)
Non-smoker
84 (93.3)
45 (97.8)
39 (88.6)
Histology (cases, %)
/
Adenocarcinoma
90 (100)
46 (100)
44 (100)
Non-adenocarcinoma
0 (0)
0 (0)
0 (0)
ECOG performance status (cases, %)
0.689
0-1
79 (87.8)
41 (89.1)
38(86.4)
2-4
11 (12.2)
5 (10.9)
6 (13.6)
Stage (cases, %)
<0.001
I-III
49 (54.4)
46 (100)
3 (6.8)
IV
41 (45.6)
0 (0)
41 (93.2)
Metastasis (cases, %)
<0.001
Absent
49 (54.4)
46 (100)
3 (6.8)
Present
41 (45.6)
0 (0)
41 (93.2)
Brain metastasis
13 (14.4)
0 (0)
13 (29.5)
Bone metastasis
24 (26.7)
0 (0)
24 (54.5)
Multi-organ metastases
20 (22.2)
0 (0)
20 (45.5)
ALK aberrations (cases, %)
0.489
Rearrangement free Uncertain aberration
1 (1.1)
0 (0)
1 (2.3)
ALK rearrangement
89 (98.9)
46 (100)
43 (97.7)
Distribution of rearrangements (cases, %)
Intergenic sequence-ALK fusion
15 (16.9)
9 (19.6)
6 (14.0)
0.480
Non-EML4-ALK fusion
18 (20.2)
10 (21.7)
8 (18.6)
0.713
EML4-ALK fusion
Variant 1
26 (29.2)
12 (26.1)
14 (32.6)
0.502
Variant 2
4 (4.5)
3 (6.5)
1 (2.3)
0.658
Variant 3
30 (33.7)
14 (30.4)
16 (37.2)
0.499
Other variants
11 (12.4)
8 (17.4)
3 (7.0)
0.136
Status of coexisting ALK fusions (cases, %)
Absent
73 (82.0)
37 (80.4)
36 (83.7)
0.687
Intergenic sequence-ALK fusion alone
5 (5.6)
2 (4.3)
3 (7.0)
0.938
Non-EML4-ALK fusion alone
8 (9.0)
5 (10.9)
3 (7.0)
0.787
EML4-ALK fusion alone
60 (67.4)
30 (65.2)
30 (69.8)
0.647
Present
16 (18.0)
9 (19.6)
7 (16.3)
0.687
Intergenic sequence-ALK fusion + EML4-ALK fusion
6 (6.7)
4 (8.7)
2 (4.7)
0.736
Intergenic sequence-ALK fusion + non-EML4-ALK fusion
1 (1.1)
1 (2.2)
0 (0)
1.000
EML4-ALK fusion + non-EML4-ALK fusion
3 (3.4)
1 (2.2)
2 (4.7)
0.953
Intergenic-ALK fusion + EML4-ALK fusion+ non-EML4-ALK fusion
2 (2.2)
2 (4.3)
0 (0)
0.495
Intergenic-ALK fusion + intragenic-ALK fusion + non-EML4-ALK fusion
1 (1.1)
0 (0)
1 (2.3)
0.483
non-EML4-ALK fusion + non-EML4-ALK fusion
3 (3.4)
1 (2.2)
2 (4.7)
0.953
Table 2 Multivariate Cox Analysis
Conclusion
This is the first to report the occurrence rates and distribution of intergenic–ALK and coexisting of ALK fusions. Intergenic–ALK and non-EML4–ALK were more likely to coexist with other fusions. Neither the type nor number of rearrangements had a significant effect on the therapeutic benefit of treatment with crizotinib.
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P86 - Targeted Therapy - Clinically Focused - New Target (ID 263)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P86.06 - A Phase I Study of Anlotinib Combined with Platinum-Pemetrexed in Untreated Non-Squamous Non-Small Cell Lung Cancer (ID 3168)
00:00 - 00:00 | Presenting Author(s): Meijuan Huang
- Abstract
Introduction
Anlotinib is a novel multi-target angioenesis tyrosine kinase inhibitor (TKI) and the ALTER0303 trial has shown that anlotinib improved survival outcomes in advanced NSCLC patients (pts) as third-line or further therapy. This dose exploration study aims to establish the feasibility profile of anlotinib in combination with chemotherapy in non-squamous NSCLC.
Methods
Untreated pts with histologically confirmed stage IIIB/IIIC/IV non-squamous NSCLC and without known sensitizing EGFR/ALK/ROS1 alterations were included. Following a 3+3 dose-reduction design, patients initially received anlotinib 12mg on days 1-14 of 21-day cycles, with either cisplatin 75 mg/m2 or carboplatin (AUC=5) plus pemetrexed 500 mg/m2 for 4 cycles. The primary objective was to identify the maximum tolerated dose (MTD) where dose-limiting toxicities (DLTs) were not observed.
Results
Between April 2019 and November 2019, a total of eight pts were enrolled to the study. DLTs were observed in two pts at anlotinib 12mg (grade 3 hand-foot syndrome, grade 3 appetite loss). No DLTs occurred in pts with anlotinib 10mg and the MTD was defined as 10mg. Among 7 pts evaluable, 6 exhibited tumor shrinkage (shrinkage range: -11.0% to -65.9%). Four of them achieved confirmed partial response (PR) and three had stable disease (SD). The overall response rate (ORR) and disease control rate (DCR) were 57.14% and 100.00%, respectively. With a median follow-up of 10.05 months, the median progression-free survival (PFS) was 7.00 months (95%CI: 2.76 to NE). Grade 3 treatment-related adverse events (TRAEs) included appetite loss (n=2), hypertension (n=2), thrombocytopenia (n=1), diarrhea (n=1) and hand-foot syndrome (n=1). No grade 4 or grade 5 TRAEs occurred during the treatment.
Conclusion
The combination therapy is well tolerated up to anlotinib 10mg and shows promising activity in untreated NSCLC patients.
